Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia (MILESTONE)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Alabama at Birmingham
About this trial
This is a phase II interventional study evaluating the use of minimal residual disease by next generation sequencing to defer autologous hematopoietic stem cell transplantation (AHCT) in patients with newly diagnosed multiple myeloma (cohort A) and amyloidosis (cohort B).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age >18 years with no upper age limit with a diagnosis of newly diagnosed multiple myeloma with indication for initiation of therapy with Eastern Cooperative Oncology Group (ECOG) performance status 0-2
No prior therapy except for dexamethasone (up to 160 mg) and/or bortezomib (up to 5.2 mg/m2 ) and/or cyclophosphamide up to 1000 mg/m2 administered for management of acute manifestations of multiple myeloma (hypercalcemia, renal impairment, pain) for no longer than 4 weeks prior to enrollment (pre induction). If subject received any prior therapy, pretreatment parameters necessary for disease characterization and response assessment must be available.
Measurable disease meeting at least one of the following criteria (at screening or prior to pre induction): 1) Serum monoclonal (M) protein ≥1.0 g/dl 2) ≥ 200 mg of M protein/24h in the urine 3) Serum free light chain ≥10 mg/dL and abnormal kappa to lambda ratio.
Life expectancy ≥ 12 months.
Disqualifiers
Diagnosis of POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes), Waldenstrom's macroglobulinemia.
Major surgery, radiotherapy or infection requiring therapy within 14 days of starting treatment.
Pregnant or lactating females.
Patients with uncontrolled human immunodeficiency virus, hepatitis B, hepatitis C. Patients may be eligible with Viral load is undetectable.
Trial design
Design model
Sequential
Treatments tested in this trial
DaraVRD/DaraVCD
DrugPatients in Cohort A with newly diagnosed multiple myeloma will receive six cycles of combination quadruplet therapy (DaraVRD). Six 28-day induction cycles of oral lenalidomide (25 mg daily on days 1-21), subcutaneous bortezomib (1.3 mg/m2 on days 1, 8, 15, 22), subcutaneous daratumumab (1800 mg on days 1, 8, 15, 22 of cycles 1-2 and days 1, 15 for cycles 3-6), and oral dexamethasone (40 mg on days 1, 8, 15, and 22). Patients in Cohort B with newly diagnosed amyloidosis will receive six cycles of combination quadruplet therapy (DaraVCD). Six 28-day induction cycles of IV cyclophosphamide (300 mg/m2 on days 1, 8, 15, 22), subcutaneous bortezomib (1.3 mg/m2 on days 1, 8, 15, 22), subcutaneous daratumumab (1800 mg on days 1, 8, 15, 22 of cycles 1-2 and days 1, 15 for cycles 3-6), and oral dexamethasone (40 mg on days 1, 8, 15, and 22).
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: Daratumumab, Bortezomib, Dexamethasone with Lenalidomide/CyclophosphamideExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of patients who are able to attain MRD<10-5 by next generation sequencing after 6 cycles of Dara-VRD and defer AHCT.
To determine the feasibility of utilizing post-induction MRD to inform transplant utilization.
Time frame
Baseline through 6 monthsSecondary outcomes
1
Number of patients who was MRD>10-5 that undergo AHCT and attain MRD<10-5.
To determine the frequency of conversion from MRD (+) to MRD (-) status with auto-HCT.
Time frame
Baseline through 10 months2
Progression free survival
To determine the progression free survival (PFS)
Time frame
Baseline through 7 years3
Overall survival
To determine the frequency of overall survival (OS)
Time frame
Baseline through 7 yearsSponsors and contacts
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Source ClinicalTrials.gov